Personalized Volumetric Tissue Generation by Enhancing Multiscale Mass Transport through 3D Printed Scaffolds in Perfused Bioreactors. Issue 24 (8th July 2022) - Forrestal, David P
Abstract: Engineered tissues provide an alternative to graft material, circumventing the use of donor tissue such as autografts or allografts and non‐physiological synthetic implants. However, their lack of vasculature limits the growth of volumetric tissue more than several millimeters thick which limits their success post‐implantation. Perfused bioreactors enhance nutrient mass transport inside lab‐grown tissue but remain poorly customizable to support the culture of personalized implants. Here, a multiscale framework of computational fluid dynamics (CFD), additive manufacturing, and a perfusion bioreactor system are presented to engineer personalized volumetric tissue in the laboratory. First, microscale 3D printed scaffold pore geometries are designed and 3D printed to characterize media perfusion through CFD and experimental fluid testing rigs. Then, perfusion bioreactors are custom‐designed to combine 3D printed scaffolds with flow‐focusing inserts in patient‐specific shapes as simulated using macroscale CFD. Finally, these computationally optimized bioreactor‐scaffold assemblies are additively manufactured and cultured with pre‐osteoblast cells for 7, 20, and 24 days to achieve tissue growth in the shape of human calcaneus bones of 13 mL volume and 1 cm thickness. This framework enables an intelligent model‐based design of 3D printed scaffolds and perfusion bioreactors which enhances nutrient transport for long‐term volumetric tissue growth in personalized implant shapes. The novel methods described here are readily applicable for use with different cell types, biomaterials, and scaffold microstructures to research therapeutic solutions for a wide range of tissues. Abstract : A biomanufacturing framework achieving personalized and volumetric lab‐grown tissue through additive manufacturing, multiscale computational fluid dynamics, and long‐term perfusion bioreactor cultivation is presented. This framework can be applied to diverse defect shapes, 3D printed scaffold patterns, and bioreactor perfusion strategies to minimize transport limitations and accomplish 60‐fold cell expansion across 3 weeks of culture in 13 mL‐volume, 10 mm‐thick scaffolds.